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Connectivity forms the basis of functional computations performed by neural circuits, but it is notoriously difficult to follow the complex structural wiring between neurons to the function of individual cells. Now, using a combination of functional imaging and three-dimensional serial electron-microscopic reconstruction at an unprecedented scale, two groups present detailed representations of the connectivity of single cells in the mouse visual system. Davi Bock et al. in Clay Reids lab investigate connectivity in the primary visual cortex, and find that inhibitory neurons receive input from excitatory cells with widely varying functions (represented on the cover by spheres and lines of different colours), consistent with predictions from recent physiological studies of the mouse cortex. Kevin Briggman, Moritz Helmstaedter and Winfried Denk show that direction-selective ganglion cells receive more synapses from a starburst amacrine cell dendrite if their preferred directions are opposites, suggesting that the directional sensitivity of retinal ganglion cells arises from the asymmetry in their wiring with amacrine cells.
An old influenza strain still circulating in birds and swine could easily jump back to humans now that immunity to it has dropped, warn Gary J. Nabel and his colleagues.
Most Europeans haven't heard of their nation's repositories of human blood and tissue samples. Promote them, say George Gaskell and Herbert Gottweis, or they could fail.
In the effort to demonstrate quantum behaviour in the motion of macroscopic mechanical objects, strong coupling between the objects and an electromagnetic oscillator is advantageous. Such coupling has now been achieved. See Letterp.204
The vitamin-A metabolite retinoic acid normally favours immune tolerance in the gut. But in coeliac disease — an intestinal inflammatory disorder due to adverse reactivity to a dietary protein — it may do just the opposite. See Letterp.220
To understand the brain, the thousands of synaptic connections made by each of billions of neurons should be mapped and related to neuronal function. First steps towards this formidable goal are now reported. See Articlesp.177 & p.183
Using a microfluidic device, tiny polymeric capsules have been made in which different compounds can be isolated in separate, membrane-bound compartments — a prerequisite for the development of artificial cell aggregates.
The parasitic infection mucocutaneous leishmaniasis can vary in severity. It emerges that the levels of an RNA virus within the parasite affect both the host's immune response and the parasite's persistence.
Initiation of the great 2010 Chile earthquake occurred within the rupture zone of the 1835 event experienced by Charles Darwin. However, the peak fault slip was to the north of the epicentre — not where it was expected to occur.
To date, various aspects of connectivity have been inferred from electron microscopy (EM) of synaptic contacts, light microscopy of axonal and dendritic arbors, and correlations in activity. However, until now it has not been possible to relate the complex structural wiring between neurons to the function of individual cells. Using a combination of functional imaging and three-dimensional serial EM reconstruction at unprecedented scale, two papers now describe the connectivity of single cells in the mouse visual system. This study investigates the connectivity of inhibitory interneurons in primary visual cortex.
To date, various aspects of connectivity have been inferred from electron microscopy (EM) of synaptic contacts, light microscopy of axonal and dendritic arbors, and correlations in activity. However, until now it has not been possible to relate the complex structural wiring between neurons to the function of individual cells. Using a combination of functional imaging and three-dimensional serial EM reconstruction at unprecedented scale, two papers now describe the connectivity of single cells in the mouse visual system. This study examines how the selectivity of directionally selective retinal ganglion cells may arise from their asymmetry in the wiring with amacrine cells.
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
The harmonic oscillator is a simple and ubiquitous physical system. This paper reports a new realization in the quantum regime, achieving direct controllable coupling between quantized mechanical oscillators. The oscillators are ions held in trapping potentials (separated by 40 micrometres) and coupled through their mutual Coulomb interaction. The system could be used as a building block for quantum computers and simulators.
A quantum mechanical link between two mechanical oscillators has never been directly demonstrated. This study achieves direct coupling between single ions oscillating in traps separated over a distance of 54 micrometres. Additional ions are employed as antennae to amplify the coupling. The system may provide a building block for quantum computers and opportunities for coupling different types of quantum systems, such as trapped Rydberg atoms.
There is a strong drive towards observing quantum effects in macroscopic mechanical systems, as this could lead to new insights in quantum-limited measurements as well as test fundamental questions regarding the impossible consequences of quantum physics at a macroscopic scale. To obtain sufficiently long-lived mechanical states the usual approach is to couple a mechanical oscillator to an electromagnetic resonance in a cavity. This study presents a new design for such a system where a free-standing flexible aluminium membrane (like a drum) is incorporated in a cavity defined by a superconducting circuit, and demonstrates a coupling strength that is two orders of magnitude higher than achieved before. The approach shows the way to observing long-lived quantum states that could survive for hundreds of microseconds.
Coarse-resolution palaeoclimate proxy evidence has suggested that the Pliocene warm period (∼3–5 million years ago) was characterized by permanent El Niño conditions in which the equatorial Pacific was uniformly warm, instead of having the modern-day 'cold tongue' extending westward from South America. This study uses high-resolution climate proxy information from fossil corals to challenge this assertion and shows that ocean conditions in the western Pacific during the Pliocene warm period were characterized by El Niño variations similar to modern-day variations.
This study shows that a dynamic two-stage model can unify a wide range of apparently contradictory observations from both large plutonic bodies and volcanic systems by a mechanism of rapid remobilization, or 'unzipping', of highly viscous crystal-rich mushes. This remobilization can lead to rapid overturn and produce the observed juxtaposition of magmatic materials with very disparate ages and complex chemical zoning. The agreement between calculated and observed unzipping rates for historical eruptions at Pinatubo and Montserrat demonstrates the potentially wide applicability of the model.
This study searched for putative regulatory mutations specific to the human lineage by looking for sequences that are highly conserved between chimpanzees and other species, but are not present in the human genome. The 500-odd human-specific deletions tend to lie in non-coding DNA stretches and near genes involved in steroid hormone signalling and neural function. This is illustrated with two examples, one of which affects penile anatomy whereas the other affects brain size.
The vitamin A metabolite retinoic acid is shown to act in conjunction with IL-15 to induce IL-12p70 production by intestinal dendritic cells, thereby promoting an inflammatory T-cell response to dietary antigens. The mechanism may underlie coeliac disease pathogenesis.
Long QT syndrome (LQTS) is a life-threatening congenital arrhythmogenic disease. This study models type-2 LQTS, which is caused by a mutation in the potassium-channel-encoding KCNH2 gene, by using induced pluripotent stem cell technology to generate cardiomyocytes from the fibroblasts of an individual diagnosed with the syndrome. The cells were used to screen a variety of drugs for either amelioration or aggravation of the disease phenotype, demonstrating the power of this approach for drug development and for patient-specific safety screening.
A mutation in the gene CACNA1C, encoding the L-type calcium channel CaV1.2 in humans, causes Timothy syndrome, a disorder characterized by autism, syndactyly, immune deficiency and cardiac arrhythmias. This study generated induced pluripotent stem cells from the fibroblasts of two patients with Timothy syndrome and converted them into cardiac cells. The patient cells displayed abnormal electrical and calcium signalling properties, which were restored by a drug, roscovitine, known to increase the voltage-dependent inactivation of CaV1.2.
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
In the nucleus, a complex of DNA ligase III (Lig3) and Xrcc1 catalyses the last step of base excision repair. Inactivation of Lig3 in the mouse leads to early embryonic lethality, but the critical role played by Lig3 in viability is unknown. This study shows, using conditional knockouts of Lig3 in the nervous system and cardiac muscle, that its essential function is maintenance of mitochondrial DNA integrity. The results also indicate distinct functional roles for Lig3 and Xrcc1.
Eukaryotic cells have several DNA ligases. DNA ligase III (Lig3) forms a complex with Xrcc1 that can function in nuclear repair. But, Lig3 null animals cannot be made; is this nuclear role in base excision repair its critical function? This is one of two papers showing that the role of Lig3 in the nucleus is non-essential. Rather, the catalytic activity of Lig3, but not Xrcc1, is essential for the maintenance of mitochondria.
During gene transcription, RNA polymerase (Pol) II moves forward along DNA and synthesizes mRNA. However, Pol II can also move backwards and stall, which is important for regulatory purposes or when the polymerase hits an obstacle such as a nucleosome. This arrested state is reactivated by the transcription factor TFIIS. Here, a crystal structure is presented of a backtracked yeast Pol II complex in which the backtracked RNA can be observed, plus a structure of a backtracked complex that contains TFIIS. A model is presented for Pol II backtracking, arrest and reactivation during transcription elongation.